Expression of four cancer-testis antigens in TNBC indicating potential universal immunotherapeutic targets

Jie Xiao1, Fengli Huang2, Lin Li3

  • 1Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.

Abstract

Insights

Cancer-testis antigens (CTAs) like MAGE-A4 and PRAME are highly expressed in triple-negative breast cancer (TNBC). Their expression correlates with longer disease-free survival, suggesting potential for immunotherapy.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Immunotherapy offers a promising avenue for breast cancer treatment.
  • Cancer-testis antigens (CTAs) are selectively expressed in tumors, making them ideal immunotherapy targets.
  • Investigating CTA expression in breast cancer is crucial for identifying effective therapeutic strategies.

Purpose of the Study:

  • To examine the expression patterns of specific CTAs in breast cancer tissues.
  • To assess the prognostic value of CTA expression for patient outcomes.
  • To identify a potential panel of CTAs for universal breast cancer immunotherapy.

Main Methods:

  • Immunohistochemistry was used to evaluate MAGE-A4, MAGEA1, NY-ESO-1, KK-LC-1, and PRAME expression in 137 breast cancer specimens, including 51 triple-negative breast cancer (TNBC) cases.
  • Expression of PD-L1 and tumor-infiltrating lymphocytes (TILs) were quantified and correlated with CTA expression.
  • Clinical data were analyzed for prognostic significance, with validation using the Kaplan-Meier plotter.

Main Results:

  • MAGE-A4, NY-ESO-1, and KK-LC-1 showed significantly higher expression in TNBC compared to non-TNBC.
  • Over 76% of TNBC cases expressed at least one of the five investigated CTAs.
  • Positive expression of MAGE-A4 or PRAME was associated with significantly extended disease-free survival (DFS), confirmed by Kaplan-Meier analysis.

Conclusions:

  • MAGE-A4, NY-ESO-1, PRAME, and KK-LC-1 are frequently overexpressed in breast cancer, particularly in TNBC.
  • MAGE-A4 and PRAME expression may serve as predictive biomarkers for prolonged DFS in breast cancer patients.
  • A curated panel of CTAs represents a promising strategy for developing universal immunotherapeutic targets for breast cancer.

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